Genetic Variant ALG13:c.-27G>A (chrX-111681192-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001099922.3(ALG13):c.-27G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,200,470 control chromosomes in the GnomAD database, including 1 homozygotes. There are 46 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., 26 hem., cov: 24)

Exomes 𝑓: 0.000061 ( 1 hom. 20 hem. )

Consequence

ALG13
NM_001099922.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.412

Publications

1 publications found

Variant links:

Genes affected

ALG13 (HGNC:30881): (ALG13 UDP-N-acetylglucosaminyltransferase subunit) The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ALG13 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 36
Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ALG13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-111681192-G-A is Benign according to our data. Variant chrX-111681192-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 387669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000621 (70/112686) while in subpopulation AFR AF = 0.00212 (66/31107). AF 95% confidence interval is 0.00171. There are 0 homozygotes in GnomAd4. There are 26 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 26 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG13	NM_001099922.3	MANE Select	c.-27G>A	5_prime_UTR	Exon 1 of 27	NP_001093392.1	Q9NP73-1
ALG13	NM_001257231.2		c.-327G>A	5_prime_UTR	Exon 1 of 27	NP_001244160.1	Q9NP73-3
ALG13	NM_001324292.2		c.-27G>A	5_prime_UTR	Exon 1 of 26	NP_001311221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG13	ENST00000394780.8	TSL:2 MANE Select	c.-27G>A	5_prime_UTR	Exon 1 of 27	ENSP00000378260.3	Q9NP73-1
ALG13	ENST00000371979.7	TSL:1	c.-27G>A	5_prime_UTR	Exon 1 of 4	ENSP00000361047.3	Q9NP73-2
ALG13	ENST00000927365.1		c.-27G>A	5_prime_UTR	Exon 1 of 27	ENSP00000597424.1

Frequencies

GnomAD3 genomes

AF:

0.000621

AC:

AN:

112632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000928

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000198

AC:

AN:

182204

AF XY:

0.000165

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000607

AC:

AN:

1087784

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

354180

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

26193

American (AMR)

AF:

0.000171

AC:

AN:

35153

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19291

East Asian (EAS)

AF:

0.00

AC:

AN:

30123

South Asian (SAS)

AF:

0.00

AC:

AN:

53881

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40474

Middle Eastern (MID)

AF:

0.000487

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.00000961

AC:

AN:

832774

Other (OTH)

AF:

0.0000437

AC:

AN:

45788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000621

AC:

AN:

112686

Hom.:

Cov.:

AF XY:

0.000746

AC XY:

AN XY:

34850

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

31107

American (AMR)

AF:

0.0000927

AC:

AN:

10783

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3530

South Asian (SAS)

AF:

0.00

AC:

AN:

2729

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6206

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53245

Other (OTH)

AF:

0.00

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000699

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.41

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over